The proposed research deals with the mechanisms which regular anatomical and physiological plasticity in the dentate gyrus of the rat hippocampus. The major group of studies concerns the factors which restrict the sprouting of the commissural-associational projections into the middle and outer molecular layer of the dentate gyrus after these zones have been deafferented by removal of their primary input, the fibers of the entorhinal cortex. The strategy to be followed consists of precisely identifying the developmental age at which restrictions on growth are imposed (sprouting in this system is essentially unlimited in immature rats) and then ascertaining if certain potentially restrictive anatomical events include: 1) astroglial hypertrophy and limited migration, 2) the "microglial" proliferation response, 3) persistent axonal degeneration. An investigation into the existence of possible biochemical factors which regulate growth and their development will also be conducted. It is felt that these experiments should provide data on the ontogeny of the dentate gyrus and could provide answers to the nature of axonal growth regulation in the adult. Ongoing work on the quantification of the fine (ultrastructural) anatomy of a particular region of the inner molecular layer will also be continued. These data will be used to study sprouting in this area after removal of its commissural afferents and to analyze any anatomical changes which correlate with the appearance of long term potentiation.